A Single Arm, Open Label, Dose-escalating, Prospective Phase I Clinical Trial Evaluating the Safety, Tolerability and Efficacy of TMT101 Injection Alone in Patients With Advanced Pancreatic Cancer or Non-small Cell Lung Cancer(NSCLC) After Standard Treatment Failure
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a first-in-human, single-arm, open-label, dose escalation prospective phase I clinical study to evaluate the Safety, Tolerability and Efficacy of TMT101 Injection Alone in patients with Unresectable, Metastatic or Advanced pancreatic cancer or Non-small Cell Lung Cancer(NSCLC) after Standard Treatment Failure. The primary objective is to evaluate the safety and tolerability of TMT101 Injection as monotherapy in patients with advanced pancreatic cancer and NSCLC, and to determine the recommended therapeutic dose (RD) of TMT101 Injection as monotherapy
详细描述
The dose escalation trial adopts the "3+3" design , and about 3~6 patients with advanced pancreatic cancer or non-small cell lung cancer are enrolled in each dose level to evaluate the safety of TMT101 Injection alone. Three dose levels are planned to be explored: 0.1 mg, 0.2 mg, and 0.4 mg. Once a week, intramuscular Injection , a total of 9 times (the first tumor assessment is performed in the 6th week (±7 days), the investigator can decide the follow-up medication arrangement according to the tumor evaluation results). Dose-limiting toxicities (DLTs) will be assessed for each dose level, and the DLT observation period will be within 21 days from the first dose. The initial dose is 0.1 mg with a dose reduction for safety reasons, the level of dose reduction will be discussed jointly between the investigator and the sponsor. If the highest dose level of 0.4 mg is not confirmed as a possible recommended therapeutic dose (RD), it may be escalated a higher dose to determine the possible RD under the condition that investigator and the sponsor to decide together
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Agrees to follow the trial protocol and visit schedule, has signed informed consent;
- •Subjects must be ≥18 years of age at time of informed consent,regardless of gender;
- •Patients with advanced/unresectable or metastatic pancreatic cancer or non-small cell lung cancer that requires histologically and/or cytologically confirmed according to the American Joint Committee on Cancer 8th edition; pancreatic cancer:Previous failure or intolerance of two or more lines of chemotherapy; NSCLC:Previous failure or intolerance of platinum-containing chemotherapy and anti-PD-1/PD-L1 monoclonal antibodies, regardless of combination therapy or sequential therapy, if the previous test for EGFR-sensitive mutations or ALK fusion genes is positive, treatment with a third-generation TKI must be failed or intolerant;
- •At least one evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
- •Estimated life expectancy≥12 weeks;
- •Adequate organ function, meet the following laboratory standards:
- •ANC≥1.5×109/L;PLT≥90×109/L;
- •TBIL≤1.5×ULN, Patients with Gilbert's syndrome ; without liver metastases, AST and ALT ≤ 2.5×ULN;liver metastases, AST and ALT ≤5×ULN ;
- •Ccr≥50 mL/min;
- •INR≤1.5×ULN, APTT≤1.5×ULN;
- •Males of childbearing potential and females of childbearing potential who are willing to use effective contraception since signing the informed consent until 6 months after the last dose of the trial drug. Females of childbearing potential must have a negative pregnancy test result within 7 days prior to the first dose.
排除标准
- •Allergic to TMT101 Injection or any of the components in the prescription;
- •Uncontrolled illness including, but not limited to, active infection requiring systemic therapy, uncontrolled hypertensionuncontrolled hyperglycemia, decompensated congestive heart failure , unstable angina, arrhythmias that require clinical intervention; ascites or uncontrolled pleural effusion (CTCAE 5.0≥grade 2), thrombosis (such as pulmonary embolism, cerebral infarction, myocardial infarction) or history of stroke, active autoimmune disease, psychiatric disease, active peptic ulcer disease, active bleeding disorder, which would limit compliance with study requirements or impair the patient's ability to sign informed consent in writing;
- •Patients who used immunosuppressive drugs within 3 weeks prior to the first dose, or patients who have achieved immunosuppressive intent (dose > 10 mg/day prednisone or other equivalent hormones and the duration of use is at least 7 days ) on systemic hormonal therapy or absorbable topical hormonal therapy, with the exception of physiologic doses of intranasal and inhaled corticosteroids;
- •Within 4 weeks prior to the first administration, received major surgery, radiotherapy (except palliative radiotherapy for bone metastasis), or treatment for surgical wounds that were not healed, ulcerated, or fractured; within 4 weeks prior to the first administration or within 5 half-lives (whichever is shorter) received anti-tumor treatments such as chemotherapy, biological therapy, endocrine therapy, targeted therapy, or immunotherapy.
- •Patients with prior or concurrent occurrence of other malignancies, with the following exceptions: a) Carcinoma in situ of the cervix or breast, curatively treated with no signs of recurrence for at least 3 years prior to the study; b) The primary malignancy was completely resected and in complete remission for ≥ 5 years;
- •History of interstitial lung disease or current interstitial lung disease or suspected of such disease by imaging during screening. and pneumonitis that previously required systemic corticosteroid treatment;
- •Treponema pallidum antibody or human immunodeficiency virus (HIV) antibody positive, positive for hepatitis C virus antibody and hepatitis C virus (HCV) RNA, or active hepatitis B (positive for hepatitis B surface antigen and HBV DNA ≥ upper limit of normal);
- •Received live vaccines within 4 weeks before the first dose or planned to receive live vaccines during the study period and within 4 weeks after the last dose, including but not limited to: measles, mumps, rubella, chickenpox, yellow fever, rabies, BCG and typhoid vaccines;
- •History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
- •Interventional therapy in other clinical trials 3 weeks before the first dose, and it is judged by the investigator and medical monitor to be unsuitable for inclusion in the study;
- •Patients who have had a previous ≥grade 3 immune-related adverse event or immunotherapy-related serious adverse event (SAE) leading to permanent discontinuation;
- •Pregnant or lactating females;
- •In the opinion of the investigator, the subject has other conditions that may affect compliance or are not suitable for participation in this study;
- •Patient has active central nervous system metastases (with or without treatment), including symptomatic brain metastases or meningeal metastases or spinal cord compression, but asymptomatic brain metastases except;
- •Within 4 weeks prior to the first dose, all toxicities from prior antineoplastic therapy have not recovered to grade 1 or less, with the following exceptions: a. alopecia, b. long-term toxicity caused by radiotherapy, c. other toxicities that cannot be recovered in the judgment of the investigator but have no effect on the subject's administration
- •Major surgery within 4 weeks prior to the first dose;
- •Transsplenectomy which is not suitable is judged by the investigator.
研究组 & 干预措施
TMT101 Injection monotherapy
Three dose levels are planned to be explored: 0.1 mg, 0.2 mg, and 0.4 mg. The initial dose is 0.1 mg with a dose reduction for safety reasons, the level of dose reduction will be discussed jointly between the investigator and the sponsor. TMT101 will be injected intramuscularly, Once a week,a total of 9 times
干预措施: TMT101 Injection (Biological)
结局指标
主要结局
dose-limiting toxicities (DLTs)
时间窗: within 21 days since the first dose
Occurrence of dose-limiting toxicities (DLTs) within 21 days since the first dose
treatment-emergent adverse events (TEAEs)
时间窗: up to 2 years
occurrence of treatment-emergent adverse events (TEAEs) and grade according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
treatment related adverse event (TRAE)
时间窗: up to 2 years
Occurrence and grade of treatment related adverse event (TRAE) according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
immune-related Adverse Event(irAE）
时间窗: up to 2 years
Occurrence and grade of immune-related Adverse Event(irAE）according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Serious Adverse Event(SAE）
时间窗: up to 2 years
Occurrence and grade of Serious Adverse Event(SAE）according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Recommended Dose（RD）
时间窗: the whole escalation phase within 21 days since the first dose
During the dose escalation phase, the MTD and/or available safety, biomarker, and efficacy data will be evaluated thoroughly to determine the RD of TMT101 Injection alone . Three dose levels are planned to be explored: 0.1 mg, 0.2 mg, and 0.4 mg. Once the initial dose is 0.1 mg with a dose reduction for safety reasons, the level of dose reduction will be discussed jointly between the investigator and the sponsor. If the highest dose level of 0.4 mg is not confirmed as a possible recommended therapeutic dose (RD), it may be escalated to a higher dose to determine the possible RD under the condition that investigator and the sponsor to decide together.
次要结局
- Objective response rate (ORR)(up to 2 years)
- Disease control rate (DCR)(up to 2 years)
- Progression-free survival (PFS)(up to 2 years)
- Overall survival (OS)(up to 2 years)
- Peak time (Tmax) of cationic lipids(up to 9 weeks)
- Peak concentration (Cmax) of cationic lipids(up to 9 weeks)
- Area under the drug concentration -time curve (AUC) of cationic lipids(up to 9 weeks)
研究者
Wu Wenming
Director, Chief Physician of Basic Surgery, Principal Investigator, Clinical Professor
Peking Union Medical College Hospital